Malaria is the one of the leading causes of death in the world. It’s an important problem to solve. So important that the Bill and Melinda Gates foundation has dedicated billions of dollars to the cause.

But we havent fixed it yet. Why not?

As with every disease, It starts with what malaria has evolved to do. The lifecycle of malaria requires both a mosquito and a human. The disease starts inside a female mosquito, jumps to a human host for a while mucking about, and then jumps back to a different mosquito.

Like the common cold, malaria doesn’t instantly kill its host. If malaria killed its host, it wouldn’t last long enough to transmit to the next host. Since it require both a mosquito and a human host, the disease stops working if it isn’t constantly jumping around. This means malaria must be good at least two things: going undetected and keeping its host moving. The longer it can stay in the current host, the more likely it’ll get passed along to the next one. It turns out malaria is really, really good at this.

Malaria has lots of tricks to stay under the radar. Think of it like a stealthy assassin that’s infiltrated your city. You know someone is killing your civilians, but you can’t figure out who. When you have malaria, your body is trying to tackle this problem. We often use vaccinations to aid our bodies in solving this problem. But why don’t we have a malaria vaccine?

It’s important to understand how vaccinations work. There are four top strategies used today:

Put a dead bugger in the body.

Put a neutered bugger in the body.

Put the bugger’s coat (a virus-like particle) in the body.

Put the bugger’s perfume (a protein marker) in the body.

All four of these strategies work the same way. Your body recognizes an intruder and teaches itself how to eliminate the threat. With a vaccine, you teach your body what signs to look for in a disease. It’s like equipping the police of your city with the physical description of the assassin. But for malaria it’s a different story.

We know that malaria relies on going undetected. It needs to transmit from host to host to operate correctly. Malaria uses stealth to render the first two strategies ineffective. Introducing dead or neutered buggers into the body doesn’t give the immune system enough information to respond when the real deal comes by.

We can’t use the third strategy because Malaria isn’t a virus. Viruses are organic robots that use some mechanical parts to inject their DNA into other cells. You can identify them by their distinctive exterior. Our third vaccination strategy doesn’t apply when we’re dealing with a non-virus disease.

That leaves us with only one option: a subunit vaccine.

A subunit vaccine works by taking the “smell” of a disease and giving it to the body. The immune system will then respond to anything with the “smell” with a heightened response. It’s like giving the police of your city a bottle of perfume and telling them to interrogate anyone smelling of it. These are difficult vaccines to put together. Proteins, like perfume, are a carefully constructed work of art and are hard to replicate perfectly. The body can get confused since it’s only given a small, complex piece of information to work with. This can render the immune system response ineffective.

It only gets worse. The malaria bugger goes through three different life stages while in the body. If targeted at the late stage, malaria has already done enough damage to kill the human host. The ideal is to target the early stage, preventing transmission and protecting the human from symptoms. Unfortunately, the first stage only lasts 5 minutes. If the body fails to identify the bugger and kick its ass in that time frame it effectively vanishes from sight.

So we have an assassin entering our city. We are already doing everything we can to destroy his transportation before he enters our borders (spraying DEET to kill mosquitos). We have a short time window to catch him before he masquerades as a citizen. If we fail in that time we will never find him. So our only option is to look for signs of a spy and ruthlessly eliminate anything that fits the bill.

It turns out there’s a vaccine called RTS,S/AS01 and that’s precisely what it does. In the 80s we were able to produce a protein from the malaria sporozoite (the first stage inside the human body) to get a small level of immunity in humans. The problem since then has been ramping up the immune response. The body needs to act fast (within 5 minutes of being infected) and with extreme prejudice (wiping out the sporozoites) using very little training (a single sporozoite protein). That’s hard. Then we have to vet this vaccination which requires human field testing in Africa. That’s even harder. Since that breakthrough in the 80s, researchers have been working hard to get the vaccination into a safe, sustainable condition. In 2012 they are really close, but still have a ways to go.

The problem with malaria is that it’s tricky. It’s taken time and some of the smartest people in the world to solve it. With RTS,S/AS01 we are nearly there. This vaccine is the culmination of 50 years of dedication, research, and hard work. It’s also a miracle of modern science. Most importantly, it will save millions of human lives.